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Journal de Mycologie Medicale Sep 2021The aim of the present study was to evaluate the in vitro susceptibility of anidulafungin, caspofungin, fluconazole and conventional amphotericin B against biofilms and...
In vitro activity of anidulafungin, caspofungin, fluconazole and amphotericin B against biofilms and planktonic forms of Candida species isolated from blood culture in patients with hematological malignancies.
OBJECTIVE
The aim of the present study was to evaluate the in vitro susceptibility of anidulafungin, caspofungin, fluconazole and conventional amphotericin B against biofilms and planktonic forms of Candida species isolated from blood culture in patients with hematological malignancies.
MATERIALS AND METHODS
Antifungal susceptibility for planktonic forms and biofilms of Candida was determined by broth microdilution method as described by Clinical and Laboratory Standards Institute M27 methodology and metabolic XTT-based [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay, respectively.
RESULTS
A total of 75 Candida isolates were evaluated between 2006-2018 yy at the National Research Center for Hematology, Russia, Moscow. Biofilm production was detected in 34 (45.3%) Candida species. Antifungal susceptibility was tested for 27 common species of Candida forming biofilms (8 C.krusei, 7 C.tropicalis, 7 C.albicans, 5 C.parapsilosis). MICs below the susceptibility breakpoints were found for 100% of planktonic forms of Candida species for anidulafungin, 85.2% for caspofungin, and 66.7% for fluconazole. Amphotericin B MIC for Candida species were less than or equal to 1 μg/ml. Candida biofilms were susceptible in vitro for both tested echinocandins, but MIC of anidulafungin were lower compared to caspofungin. The highest MIC against Candida biofilms was found for fluconazole (>1,024 μg/ml for all tested isolates) and for conventional amphotericin B (range 4-16 μg/ml).
CONCLUSION
The majority of Candida isolates grown as planktonic forms were susceptible to anidulafungin, caspofungin, conventional amphotericin B and fluconazole. Anidulafungin displayed higher activity against Candida biofilms than caspofungin. All Candida biofilms were resistant to fluconazole and conventional amphotericin B.
Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Biofilms; Blood Culture; Candida; Caspofungin; Echinocandins; Fluconazole; Hematologic Neoplasms; Humans; Microbial Sensitivity Tests; Plankton
PubMed: 34147758
DOI: 10.1016/j.mycmed.2021.101162 -
Farmacia Hospitalaria : Organo Oficial... Sep 2019To determine by experimentation whether micafungin and anidulafungin possess physicochemical properties suitable for nebulization.
OBJECTIVE
To determine by experimentation whether micafungin and anidulafungin possess physicochemical properties suitable for nebulization.
METHOD
PH, osmolality, viscosity, density and chloride content were determined by pH monitoring, osmometry, viscometry, densitometry and potentiometry in two samples of different concentrations, 5 and 10 mg/mL each echinocandin. Results: The results obtained for micafungin solution were: pH 5.80 (0.14), osmolality 293.33 (1.53) mOsm/kg, chloride content 134.67 (0.58) mmol/L and density 1,009.4 (0,1) kg/m3; while for 10 mg/mL solution: osmolality 342.00 (1.00) mOsm/kg, chloride content 139.67 (0.58) mmol/L and density 1,014.5 (0.2) kg/m3. The results obtained for 5 mg/mL anidulafungin were: pH 4.22 (0.01), osmolality 464.67 (2.52) mOsm/kg, chloride content 137.00 (0.00) mmol/L and density 1,016.5 (0,2) kg/m3; while for 10 mg/mL solution: osmolality 656.33 (1.15) mOsm/kg, chloride content 132.00 (0.00) mmol/L and density 1,029.8 (0.4) kg/m3. Conclusions: PH, osmolality, chloride content and density values proved to be suitable for proper tolerability by nebulization.
Topics: Administration, Inhalation; Anidulafungin; Antifungal Agents; Chlorides; Humans; Hydrogen-Ion Concentration; Micafungin; Nebulizers and Vaporizers; Osmometry; Viscosity
PubMed: 31469629
DOI: 10.7399/fh.11226 -
Pharmacokinetics of echinocandins in suspected candida peritonitis: A potential risk for resistance.International Journal of Infectious... Dec 2020A possible increase in Candida resistance, especially in Candida glabrata, has been speculated according to poor diffusion of echinocandins to peritoneal fluid.
INTRODUCTION
A possible increase in Candida resistance, especially in Candida glabrata, has been speculated according to poor diffusion of echinocandins to peritoneal fluid.
MATERIALS/METHODS
Peritoneal and serum concentrations of caspofungin, micafungin and anidulafungin were analysed in surgical patients with suspected candida peritonitis. After 4 days of starting therapy, serum and peritoneal samples (through peritoneal drainage) were obtained at baseline, 1, 6, 12 and 24 h of drug administration. Micafungin and anidulafungin concentrations were determined using high-performance liquid chromatography (HPLC/F), whereas caspofungin concentrations were established by bioassay.
RESULTS
Twenty-three critically ill patients with suspected abdominal fungal infection who were receiving an echinocandin were prospectively recruited. No specific criteria were applied to prescribe one specific echinocandin. No special clinical differences were observed among the three groups of patients. All were receiving antibiotic therapy, 80% required inotropic drugs, and fungal peritonitis was confirmed in 74% of them. The AUC (mg × h/L) obtained in serum and peritoneal fluid were: 126.84 and 34.38, 98.52 and 18.83, and 66.9 and 8.78 for anidulafungin, micafungin and caspofungin, respectively. The median concentration in peritoneal fluid ranged from 0.66 to 1.82 μg/mL for anidulafungin, 0.68-0.88 μg/mL for micafungin and 0.21-0.46 μg/mL for caspofungin.
CONCLUSION
The results showed moderate penetration of echinocandins into the peritoneal fluid of these patients. These levels are below the threshold of resistance mutant selection published by other authors. This could justify a potential risk of resistance in patients with prolonged treatment with echinocandins and suboptimal control of abdominal infection.
Topics: Adult; Anidulafungin; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Critical Illness; Echinocandins; Female; Humans; Male; Micafungin; Microbial Sensitivity Tests; Peritonitis; Prospective Studies
PubMed: 32937195
DOI: 10.1016/j.ijid.2020.09.019 -
Scientific Reports May 2021Cytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to...
Cytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham extracorporeal circuit (controls) and to drug combinations (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circuit) was performed over six hours following administration. Total clearance and adsorber-specific clearance were computed. Hemoadsorption was associated with increased clearance of all study drugs, except ganciclovir. Its impact on total body clearance was considered as moderate for fluconazole (282%) and linezolid (115%), mild for liposomal amphotericin B (75%), posaconazole (32%) and teicoplanine (31%) and negligible for all other drugs. Hemoadsorber clearance declined over time, with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p = 0.01; r = 0.43). Hemoadsorption with CytoSorb appears to increase to a clinically significant extent the clearance of five among 17 tested anti-infectives. Studies in human patients are required to confirm the need for dosage adjustment of these agents.
Topics: Adsorption; Animals; Anti-Infective Agents; Extracorporeal Circulation; Female; Male; Sepsis; Swine
PubMed: 34006946
DOI: 10.1038/s41598-021-89965-z -
Antimicrobial Agents and Chemotherapy Mar 2021A total of 15 isolates from the SENTRY antimicrobial surveillance program between 2006 and 2019 were combined with 21 isolates from other collections for the evaluation...
Evaluation of Synergistic Activity of Isavuconazole or Voriconazole plus Anidulafungin and the Occurrence and Genetic Characterization of Candida auris Detected in a Surveillance Program.
A total of 15 isolates from the SENTRY antimicrobial surveillance program between 2006 and 2019 were combined with 21 isolates from other collections for the evaluation of antifungal susceptibility and synergy against anidulafungin plus voriconazole or isavuconazole using the checkerboard method. Surveillance isolates were analyzed for genetic relatedness and resistance mechanisms. Applying the tentative statistical epidemiological cutoff values and the Centers for Disease Control tentative breakpoints, 32/36 isolates were resistant to fluconazole, 5/36 were resistant to amphotericin B, 5/36 were non-wild-type (NWT) to anidulafungin, 3/36 were NWT to micafungin, and 1/36 and 10/36 were NWT to isavuconazole and voriconazole, respectively. Of these, 10 isolates were multidrug resistant, which means that these isolates were resistant to 2 antifungal classes. Synergy or partial synergy was noted in 5/36 and 22/36, respectively, of the isolates with the combination of anidulafungin plus voriconazole, and 11/36 and 19/36 isolates, respectively, for the combination of anidulafungin plus isavuconazole. Multilocus sequence type (MLST) analysis of the 15 SENTRY isolates demonstrated that the isolates from the US were genetically related to, but different from, isolates from Latin America (Panama and Colombia) and Germany. Single nucleotide polymorphism (SNP) analysis showed that the 15 SENTRY isolates belonged to the described international clades and had associated Erg11 alterations, including 11 isolates displaying K143R, one displaying F126L, and one displaying Y501H alterations and a fluconazole MIC result of ≥64 mg/liter. Resistance mechanisms were not observed in the two isolates displaying fluconazole MIC values at 4 and 16 mg/liter. Isavuconazole displayed activity and greater synergy when tested with anidulafungin than seen with anidulafungin plus voriconazole against the clinical isolates that displayed resistance phenotypes.
Topics: Anidulafungin; Antifungal Agents; Candida; Colombia; Drug Resistance, Fungal; Drug Synergism; Echinocandins; Germany; Microbial Sensitivity Tests; Multilocus Sequence Typing; Nitriles; Pyridines; Triazoles; Voriconazole
PubMed: 33431416
DOI: 10.1128/AAC.02031-20 -
Indian Journal of Microbiology Mar 2022Fungi are one of the most widely distributed microorganisms in the environment, including food such as fruits, vegetables and other crops, posing a potential threat to...
Fungi are one of the most widely distributed microorganisms in the environment, including food such as fruits, vegetables and other crops, posing a potential threat to food safety and human health. The aim of this study was to determine the diversity, intensity and drug resistance of potentially pathogenic filamentous fungi isolated from the fresh raspberries ( L.). A total of 50 strains belonging to genera , , , , , , and were tested for drug resistance against 11 antifungals by disc diffusion and gradient strips methods. The average mycological contamination in the examined samples of raspberries amounted to 4.34 log CFU/g. The was isolated from all tested samples, followed by and with a frequency of 61% and 34%, respectively. The highest level of drug resistance was observed for genera and strains recorded a wide variation in drug resistance as revealed by susceptibility with amphotericin B and voriconzole with MICs ranged from 0.5-4 µg/ml and posaconazole with MICs ranging from 3-8 µg/ml. All fungal strains showed 100% resistance to caspofungin, fluconazole and flucytosine with both the methods, and 100% resistance to micafungin and anidulafungin in the gradient strip method.
PubMed: 35068614
DOI: 10.1007/s12088-021-00966-y -
Oral Surgery, Oral Medicine, Oral... Nov 2020Oral candidiasis is a common opportunistic infection that requires knowledge of the various clinical presentations and management strategies for successful treatment.... (Review)
Review
Oral candidiasis is a common opportunistic infection that requires knowledge of the various clinical presentations and management strategies for successful treatment. Numerous local and systemic factors contribute to the development of candidiasis, and the infections can range from superficial mucocutaneous overgrowths to invasive bloodstream infections with a high mortality rate. In addition to Candida albicans, various fungal strains have been isolated from the oral cavity, including C. tropicalis, C. glabrata, C. krusei, and many others. Antifungal agents are available in various forms, each with differing indications, dosing regimens, adverse effects, and drug interactions. Some antifungal agents are available as oral suspensions, pastilles, or creams, whereas others are administered systemically in capsule or intravenous form. This review describes the various presentations of oral candidiasis and the diagnostic methods and treatment alternatives, with a specific focus on pharmacologic management. Spectra of activity, mechanisms of action, adverse reactions, drug interactions, and dosing regimens are explored in the context of both topical and systemic pharmacotherapy used to treat candidiasis. Polyenes (nystatin, amphotericin B); azoles (ketoconazole, miconazole, clotrimazole, fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole); and echinocandins (caspofungin, micafungin, anidulafungin) are discussed. Novel approaches in antifungal therapy with the use of probiotics are also reviewed.
Topics: Amphotericin B; Antifungal Agents; Dentistry; Drug Resistance, Fungal; Echinocandins; Fluconazole; Microbial Sensitivity Tests
PubMed: 32907786
DOI: 10.1016/j.oooo.2020.08.011 -
Pharmaceuticals (Basel, Switzerland) Dec 2021Fission yeast contains three essential β(1,3)-D-glucan synthases (GSs), Bgs1, Bgs3, and Bgs4, with non-overlapping roles in cell integrity and morphogenesis. Only the...
Fission yeast contains three essential β(1,3)-D-glucan synthases (GSs), Bgs1, Bgs3, and Bgs4, with non-overlapping roles in cell integrity and morphogenesis. Only the mutants and exhibit resistance to GS inhibitors, even in the presence of the wild-type (WT) sequences of and . Thus, Bgs1 and Bgs3 functions seem to be unaffected by those GS inhibitors. To learn more about echinocandins' mechanism of action and resistance, cytokinesis progression and cell death were examined by time-lapse fluorescence microscopy in WT and cells at the start of treatment with sublethal and lethal concentrations of anidulafungin, caspofungin, and micafungin. In WT, sublethal concentrations of the three drugs caused abundant cell death that was either suppressed (anidulafungin and micafungin) or greatly reduced (caspofungin) in cells. Interestingly, the lethal concentrations induced differential phenotypes depending on the echinocandin used. Anidulafungin and caspofungin were mostly fungistatic, heavily impairing cytokinesis progression in both WT and . As with sublethal concentrations, lethal concentrations of micafungin were primarily fungicidal in WT cells, causing cell lysis without impairing cytokinesis. The lytic phenotype was suppressed again in cells. Our results suggest that micafungin always exerts its fungicidal effect by solely inhibiting Bgs4. In contrast, lethal concentrations of anidulafungin and caspofungin cause an early cytokinesis arrest, probably by the combined inhibition of several GSs.
PubMed: 34959732
DOI: 10.3390/ph14121332 -
Frontiers in Cellular and Infection... 2023Opportunistic fungal infections by species arise among cancer patients due to the weakened immune system following extensive chemotherapy. Prophylaxis with antifungal...
OBJECTIVE
Opportunistic fungal infections by species arise among cancer patients due to the weakened immune system following extensive chemotherapy. Prophylaxis with antifungal agents have developed the resistance of spp. to antifungals. Accurate identification of yeasts and susceptibility patterns are main concerns that can directly effect on the treatment of patients.
METHODS
Over a period of three years, 325 cancer patients suspected to infections were included in the current investigation. The clinical isolates were molecularly identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). All strains, were examined for susceptibility to the amphotericin B, itraconazole, fluconazole, and anidulafungin according to the CLSI M27 document.
RESULTS
Seventy-four cancer patients had infections (22.7%). was the most common species (83.8%). Antifungal susceptibility results indicated that 100% of the isolates were sensitive to amphotericin B; however, 17.6%, 9.4%, and 5.4% of clinical isolates were resistant to anidulafungin, fluconazole, and itraconazole, respectively.
CONCLUSION
The findings of the present work shows a warning increase in resistance to echinocandins. Since all fluconazole resistance isolates were obtained from candidemia, we recommend amphotericin B as the first line therapy for this potentially fatal infection.
Topics: Humans; Antifungal Agents; Fluconazole; Amphotericin B; Itraconazole; Anidulafungin; Microbial Sensitivity Tests; Candidiasis; Candida; Candidemia; Neoplasms; Drug Resistance, Fungal
PubMed: 37249981
DOI: 10.3389/fcimb.2023.1152552 -
BMC Microbiology Nov 2023Candida glabrata is an important cause of invasive candidiasis. Echinocandins are the first-line treatment of invasive candidiasis caused by C. glabrata. The...
BACKGROUND
Candida glabrata is an important cause of invasive candidiasis. Echinocandins are the first-line treatment of invasive candidiasis caused by C. glabrata. The epidemiological echinocandin sensitivity requires long-term surveillance and the understanding about whole genome characteristics of echinocandin non-susceptible isolates was limited.
RESULTS
The present study investigated the echinocandin susceptibility of 1650 C. glabrata clinical isolates in China from August 2014 to July 2019. The in vitro activity of micafungin was significantly better than those of caspofungin and anidulafungin (P < 0.001), assessed by MIC values. Whole genome sequencing was conducted on non-susceptible isolates and geography-matched susceptible isolates. Thirteen isolates (0.79%) were resistant to at least one echinocandin. Six isolates (0.36%) were solely intermediate to caspofungin. Common evolutionary analysis of echinocandin-resistant and echinocandin-intermediate isolates revealed genes related with reduced caspofungin sensitivity, including previously identified sphinganine hydroxylase encoding gene SUR2. Genome-wide association study identified SNPs at subtelometric regions that were associated with echinocandin non-susceptibility. In-host evolution of echinocandin resistance of serial isolates revealed an enrichment for non-synonymous mutations in adhesins genes and loss of subtelometric regions containing adhesin genes.
CONCLUSIONS
The echinocandins are highly active against C. glabrata in China with a resistant rate of 0.79%. Echinocandin non-susceptible isolates carried common evolved genes which are related with reduced caspofungin sensitivity. In-host evolution of C. glabrata accompanied intensive changing of adhesins profile.
Topics: Humans; Echinocandins; Candida glabrata; Caspofungin; Antifungal Agents; Genome-Wide Association Study; Microbial Sensitivity Tests; Candidiasis, Invasive; China; Drug Resistance, Fungal
PubMed: 37974063
DOI: 10.1186/s12866-023-03105-3